Thrombolysis in Selected Patients with Wake Up Stroke is Feasible ...

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Thrombolysis in Selected Patients with Wake Up Stroke is Feasible ...

Thrombolysis in Selected Patients with Wake

Up Stroke is Feasible with Similar Safety as

Thrombolysis in 0-4.5 Hours

Dulka Manawadu, Shankaranand Bodla,

Jozef Jarosz , Lalit Kalra

King’s College Hospital NHS Foundation Trust and

King’s College London

ISC 1/2/12


Background

• Treatment with recombinant tissue plasminogen

activator (rt-PA) significantly reduces disability. 1

• Data shows that only between 1.6 to 22% of patients

receive thrombolysis. 2,3

• Why so few? Mainly because delay to treatment or

because onset time is unknown. 4

• Unknown time of stroke onset also applies to those

with wake up stroke (WUS) which accounts for 8-27%

of all patients presenting with strokes. 5,6

1. Hacke W et al, Lancet 2004; 2. Grond M et al Stroke 1998; 3. Reed SD et al Stroke 2001;

4. Kwan J et al, Age and Aging 2004; 5. Fink JN et al Stroke 2002; 6. CASPR Investigators

Neurology 2005


Concepts

• Why exclude WUS from treatment?

– Time of onset may exceed 4.5 hours and may be

associated with little benefit but a higher risk of

intracerebral haemorrhage (ICH)

– RCT including WUS patients (Glycoprotein IIb/IIIa

inhibitor) showed higher symptomatic intracerebral

haemorrhage (sICH) in WUS (13.6% vs. 4%, p=0.07) 1

1. Adams HP Jr et al, Stroke 2008


Concepts II: why include?

• Natural history of WUS without treatment

– fewer at home 20.2% vs 44.7% p= 0.0001 1

– less ‘excellent outcome’ 6% (cf 26% placebo NINDS) 2

• Similar clinical characteristics at baseline 3-5

• Similar imaging at baseline

– MRI: DWI/PWI mismatch similar


Hypothesis

Aims and Objectives

• WUS patients who have no or minimal EICs on CT will

have comparable functional outcomes and sICH rates

to patients also receiving thrombolysis within 4.5 h

Objective

• To compare baseline characteristics and clinical

outcomes at 90 days between WUS and those

receiving thrombolysis at 0-4.5 hours


Methods

Data extracted from a registry of thrombolysed patients

• Unselected consecutive patients onset 0-4.5 hours, all ages, NIH ≥ 5

• Unselected consecutive WUS patients, all ages, NIH ≥ 5

– normal on retiring who awoke with symptoms

– exclusion from ‘WUS’ category if awoke within 4.5 hours

• Age, sex, vascular risk factors, stroke aetiology, pre-morbid modified

Rankin Scale score (mRS), BP, glucose, NIHSS score

Outcome measures:

• 24h: NIHSS and ΔNIHSS scores

• 48h: ICH, symptomatic intracerebral haemorrhage (sICH)

• 3 months: mRS score, mortality

• mRS scores assessed by certified assessors, masked to allocation


Baseline Characteristics

0-4.5 hours

N=326

Wake up stroke

N=68

p value

Mean (SD) age in years 72.8 (14.7) 73.9 (15.6) 0.58

Male (%) 155 (48%) 23 (34%) 0.045

Hypertension (%) 185 (57%) 45 (66%) 0.18

Atrial fibrillation (%) 79 (24%) 21 (31%) 0.28

Mean (SD) baseline SBP (mm Hg) 150 (26) 152 (26) 0.58

Mean (SD) baseline glucose (mmol/l) 6.5 (2.7) 6.5 (2.4) 0.79

Mean (SD) baseline NIHSS (SD) 13.4 (6.3) 12.6 (5.1) 0.34

ASPECTS 8-10 262 (80%) 58 (77%) 0.328

Hyperdense MCA sign (%) 148 (45%) 29 (43%) 0.69

Perfusion CT (%) 84 (26%) 44 (67%)


Outcomes

0-4.5 hours

(326)

WUS

(68)

p-value

Mean (SD) NIHSS at 24 hours 11.5 (9.5) 7.2 (6.9) 0.001

∆NIHSS (SD) change at 24 h -1.8 (8.1) -4.9 (5.8) 0.006

Any ICH (%) 66 (20%) 15 (22%) 0.42

sICH (%) 11 (3.4%) 2 (2.9%) 1.0

mRS 0-1 at 3 months (%) 77(23.6) 11 (16.2) 0.18

mRS 0-2 at 3 months (%) 124 (38%) 25 (37%) 0.89

Mortality at 3 months (%) 82 (26%) 10 (15%) 0.06


Baseline Characteristics

Patients aged 18-80 years

0-4.5 hours

N=197

Wake up stroke

N=33

P value

Mean (SD) age in years 64.5 (12.8) 62.7 (14.6) 0.47

Male (%) 102 (52%) 14 (42%) 0.320

Mean (SD) baseline NIHSS (SD) 13.0 (6.4) 11.7 (4.6) 0.25

ASPECTS 8-10 162 (82.2) 26 (78.8) 0.64

Hyperdense MCA sign (%) 97 (49.2) 16 (48.5) 0.94

Outcomes

Mean (SD) NIHSS at 24 hours 8.9 (8.3) 5.3 (4.6) 0.018

Mean (SD) change in NIHSS at 24 h -4.01 (7.6) -6.4 (4.6) 0.089

Any ICH (%) 35 (18%) 8 (24%) 0.377

SICH (%) 6 (3.0%) 0 (0%) 0.310

mRS 0-1 at 3 months (%) 62 (31.5) 7 (21.2) 0.234

mRS 0-2 at 3 months (%) 101 (51%) 19 (58%) 0.502

Mortality at 3 months (%) 34 (18%) 1 (3%) 0.032


mRS at 3 months


Baseline Characteristics

WUS dichotomised by age

80 years,

N=41

>80 years

N=27

P value

Male (%) 14 (34) 9 (33) 0.95

Mean (SD) SBP (mm Hg) 148 (23) 159 (29) 0.11

Mean (SD) glucose (mmol/l) 6.3 (2.2) 6.9 (2.6) 0.26

Mean (SD) NIHSS 11.8 (4.7) 13.9 (5.4) 0.102

ASPECTS 8-10 34 (83) 19 (70) 0.54

DTN (min) 1:17 1:11 0.74

Outcomes

Mean (SD) NIHSS at 24 hours 6.2 (5.6) 11.8 (8.9) 0.002

Mean (SD) change in NIHSS at 24 h -5.6 (5.4) -2.0 (6.1) 0.0014

Any ICH (%) 9 (22) 6 (22) 0.98

SICH (%) 1 (2.4) 1 (3.7) 0.76

mRS 0-2 at 3 months (%) 19 (46) 6 (22) 0.044

Mortality at 3 months (%) 2 (5) 8 (30) 0.005


Predictors of outcome

mRS 0-2 at 3 months

Age 0.94 (0.92- 0.96)

ASPECTS 3.4 (1.6-7.3)

Whole group WUS

Baseline NIH 0.88 (0.83-0.93) 0.79 (0.65-0.96)

SICH

ASPECTS 8-10 0.22 (0.06-0.84)

DBP 1.04 (0.99-1.090)

Death

Age 1.07 (1.04-1.10) 1.45 (1.07-1.95)

Baseline NIH 1.14 (1.08-1.20) 1.49 (1.04-2.14)

BG 1.21 (1.07-1.37)

WUS 0.31 (0.11-0.82)


Limitations

• Retrospective with inclusion of all cases

• Single centre

• Outcome bias:

– Trained and certified observers

– Follow-up mRS collection blinded to group

– Independent review of imaging data

– Only 9/394 (2%) patients lost to follow up at 3/12


Conclusion

Feasible and safe to thrombolyse WUS patients with

clinical and imaging features comparable to patients

within 0-4.5 hours

• The outcomes of WUS patients are comparable to 0-

4.5h group; lower mortality probably inadvertent

selection bias despite comparable baseline covariates

• Time for systematic investigation of benefit of

thrombolysis in WUS patients with early ischaemic

changes on imaging at presentation.


WUS: Does Perfusion Imaging help?

No/matched

deficits

N=27

Mismatch

N= 18

P value

Age 74.8 (12.5) 75.5 (14.9) 0.88

Male (%) 7 (26) 8 (44) 0.20

Mean (SD) baseline NIHSS (SD) 12.3 (4.7) 12.7 (5.0) 0.81

ASPECTS 8-10 24 (89) 13 (72) 0.15

Hyperdense MCA sign (%) 9 (33) 10 (55) 0.14

Outcomes

Any ICH (%) 6 (22) 5 (28) 0.67

SICH (%) 2 (7.4) 0 0.24

mRS 0-2 at 3 months (%) 10 (37) 8 (44) 0.62

Mortality at 3 months (%) 4 (15) 3 (16) 0.87

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